Update on Dengue: Epidemiology, Virus Evolution, Antiviral Drugs, and Vaccine Development
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Dengue virus is the most widespread geographically of the arboviruses and a major public health threat in the tropics and subtropics. Scientific advances in recent years have provided new insights about the pathogenesis of more severe disease and novel approaches into the development of antiviral compounds and dengue vaccines. Phylogenetic studies show an association between specific subtypes (within serotypes) and severity of dengue. The lack of association between maternal antibodies and development of severe dengue in infants in a recent study has called for the rethinking or refinement of the current antibody-dependent enhancement theory of dengue hemorrhagic syndrome in infancy. Such studies should stimulate new directions of research into mechanisms responsible for the development of severe dengue. The life cycle of dengue virus readily shows that virus entry and replication can be targeted by small molecules. Advances in a mouse model (AG 129 mice) have made it easier to test such antiviral compounds. The efforts to find specific dengue inhibitors are intensifying and the tools to evaluate the efficacy of new drugs are now in place for rapid translation into trials in humans. Furthermore, several dengue vaccine candidates are in development, of which the chimeric dengue/yellow fever vaccine has now entered phase 3 trials. Until the availability of a licensed vaccine, disease surveillance and vector population control remain the mainstay of dengue prevention.
KeywordsDengue Expansion of dengue Dengue serotypes Dengue genotypes Dengue vaccines Dengue antiviral compounds Dengue antiviral therapy Epidemiology of dengue
Dr. Wilder-Smith is the principal investigator of a Sanofi Pasteur dengue vaccine trial; received speaker honoraria and reimbursements for travel to conferences by GlaxoSmithKline, Novartis, and Sanofi Pasteur; and has served on the Novartis advisory board for travel vaccines. Dr. Gubler has received honoraria from Novartis Institute of Tropical Diseases, Invivogen, and Hawaii Biotech. No other potential conflict of interest relevant to this article was reported.
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